Variant 7-76510893-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001347684.2(UPK3B):c.86-10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,593,856 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 8 hom. )

Consequence

UPK3B
NM_001347684.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.19

Variant links:

Genes affected

UPK3B (HGNC:21444): (uroplakin 3B) UPK3B is a minor component of the apical plaques of mammalian urothelium that binds and dimerizes with uroplakin-1b (UPK1B; MIM 602380), one of the major conserved urothelium membrane proteins. The other major conserved integral membrane proteins of urothelial plaques are UPK1A (MIM 611557), UPK2 (MIM 611558), and UPK3A (MIM 611559) (Deng et al., 2002 [PubMed 12446744]).[supplied by OMIM, Mar 2008]

UPK3B links:

UPK3B (HGNC:):

UPK3B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004237652).

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UPK3B	NM_001347684.2 linkuse as main transcript	c.86-10G>A		intron_variant		ENST00000334348.8	NP_001334613.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UPK3B	ENST00000334348.8 linkuse as main transcript	c.86-10G>A		intron_variant		2	NM_001347684.2	ENSP00000334938.3	Q9BT76-3
UPK3B	ENST00000257632.9 linkuse as main transcript	c.241G>A	p.Val81Met	missense_variant	1/4	2		ENSP00000257632.5	Q9BT76-1
UPK3B	ENST00000394849.1 linkuse as main transcript	c.86-10G>A		intron_variant		2		ENSP00000378319.1	Q9BT76-2
UPK3B	ENST00000490360.1 linkuse as main transcript	n.139G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00135

AC:

205

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00235

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00107

AC:

225

AN:

209554

Hom.:

AF XY:

0.00106

AC XY:

121

AN XY:

113914

show subpopulations

Gnomad AFR exome

AF:

0.000471

Gnomad AMR exome

AF:

0.000767

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00201

Gnomad OTH exome

AF:

0.000949

GnomAD4 exome

AF:

0.00210

AC:

3030

AN:

1441590

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

1484

AN XY:

715782

show subpopulations

Gnomad4 AFR exome

AF:

0.000212

Gnomad4 AMR exome

AF:

0.000797

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000717

Gnomad4 FIN exome

AF:

0.000467

Gnomad4 NFE exome

AF:

0.00256

Gnomad4 OTH exome

AF:

0.00217

GnomAD4 genome

AF:

0.00135

AC:

205

AN:

152266

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00235

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00173

Hom.:

Bravo

AF:

0.00139

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000870

AC:

105

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.058

DANN

Benign

0.86

DEOGEN2

Benign

0.00044

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0097

LIST_S2

Benign

0.39

M_CAP

Benign

0.0030

MetaRNN

Benign

0.0042

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.21

REVEL

Benign

0.016

Sift

Benign

0.049

Sift4G

Benign

0.16

Polyphen

0.44

Vest4

0.018

MVP

0.014

ClinPred

0.0024

GERP RS

-6.0

Varity_R

0.026

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over